Structural mechanism for recognition of E2F1 by the ubiquitin ligase adaptor Cyclin F.

Cyclin F, a non-canonical member of the cyclin protein family, plays a critical role in regulating the precise transitions of cell-cycle events. Unlike canonical cyclins, which bind and activate cyclin-dependent kinases (CDKs), Cyclin F functions as a substrate receptor protein within the Skp1-Cullin-F box (SCF) E3 ubiquitin ligase complex, enabling the ubiquitylation of target proteins. The structural features that distinguish Cyclin F as a ligase adaptor and the mechanisms underlying its selective substrate recruitment over Cyclin A, which functions in complex with CDK2 at a similar time in the cell cycle, remain largely unexplored.

Migraine Genetic Susceptibility Does Not Strongly Influence Migraine Characteristics and Outcomes in a Treated, Real-World, Community Cohort.

: Migraine is a common neurological disorder with highly variable characteristics. While genome-wide association studies have identified genetic risk factors that implicate underlying pathways, the influence of genetic susceptibility on disease characteristics or treatment response is incompletely understood. We examined the relationships between a previously developed standardized integrative migraine polygenic genetic risk score (PRS) and migraine characteristics in a real-world, treated patient cohort.

Differences in binding affinity among cell-cycle CDK and cyclin pairs.

The mammalian cell cycle is coordinated by primarily four cyclin-dependent kinases (CDKs), which are activated by a family of cyclin proteins to phosphorylate diverse protein effectors of cell growth and division. A wealth of qualitative protein interaction studies have supported a model in which different CDKs have specific cognate cyclin partners. However, there have been few quantitative measurements of binding kinetics and affinity to support our understanding of CDK-cyclin preferences and the structural origins of those preferences.

Efficacy and safety of ibuprofen and naproxen in the treatment of oligoarticular juvenile idiopathic arthritis: bi-national cohort study.

Objectives: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Nonsteroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections are first-line therapy for oligoarticular JIA. NSAIDs Adverse events (AEs) include gastrointestinal ulcers/bleeding and impaired renal function.

Cross-species analyses of thymic mimetic cells reveal evolutionarily ancient origins and both conserved and species-specific elements.

Thymic mimetic cells are molecular hybrids between medullary-thymic-epithelial cells (mTECs) and diverse peripheral cell types. They are involved in eliminating autoreactive T cells and can perform supplementary functions reflective of their peripheral-cell counterparts. Current knowledge about mimetic cells derives largely from mouse models.